97P Investigation of compensatory resistance mechanisms against the FGFR inhibitor in bladder cancer cell lines

Results: OC201 and OC202e each suppressed EMT induced by TGF-/TNF-, reducing Snail, N-cadherin, and MMP-2 and restoring E-cadherin.OC201 decreased AKT and IB phosphorylation and reduced NFB nuclear localization.PKC knockdown phenocopied OC201's inhibitory effects, consistent with OC201 acting through a PKC-linked regulatory mechanism.OC202e decreased LC3B expression and inhibited autophagy-dependent support of EMT signaling.Combination treatment produced the strongest reductions in AKT/IB phosphorylation, NFB activation, and EMT progression.In vivo, both compounds significantly reduced hepatic metastatic nodules, with the combination yielding the greatest suppression.Conclusions: OC201 targets PKC-associated AKT-NFB-Snail signaling, while OC202e inhibits autophagy-mediated support of EMT.Their complementary mechanisms lead to synergistic inhibition of EMT and metastasis, supporting OC201 and OC202e combination therapy as a promising strategy for pancreatic cancer.